Preimplantation Genetic Diagnosis for Single Gene Disorders

As mentioned, preimplantation genetic diagnosis (PGD) was introduced 14 years ago with the purpose of performing genetic testing before pregnancy, in order to establish only unaffected pregnancies and avoid the need for pregnancy termination, which is the major limitation of traditional prenatal diagnosis [1, 2]. Despite the requirement for ovarian hyperstimulation and in vitro fertilization (IVF), needed to perform genetic testing of oocyte or embryo prior to transfer, PGD has been accepted in most parts of the world, with an overall number of approximately 7000 PGD cases performed by the present time, which have resulted in the birth of close to 2000 healthy children [3, 4]. At least 2000 of these PGD cycles were performed for single-gene disorders, and as will be shown below, is presently offered for some indications that have never been practiced in prenatal diagnosis, such as late-onset diseases with genetic predisposition and preimplantation HLA typing, making PGD not only an alternative but also a complement to prenatal diagnosis [4, 5]. The progress of PGD has been extensively reviewed, so the present book will mainly concentrate on those aspects of PGD that are useful for reproductive medicine and genetics practices, including available PGD approaches for different groups of genetic disorders, its accuracy, and major indications compared with prenatal diagnosis, and will present practical details useful for realization of PGD for each of the conditions described.

Indications for PGD were initially similar to those practiced in prenatal diagnosis, and applied for those at-risk couples that could not accept pregnancy termination, expected in 25-50% of cases following prenatal diagnosis, depending on the mode of inheritance. However, these indications have recently been extended beyond those for prenatal diagnosis, and currently include the conditions with a low penetrance, late-onset disorders with genetic predisposition, and HLA typing with or without testing for causative gene. The list of disorders for which PGD has been applied, according to our experience, now comprises close to 100 conditions (Table 3.1), with most frequent ones still being cystic fibrosis (CFTR), haemoglobin disorders, and some of the dynamic mutations. The choice between prenatal diagnosis and PGD mainly depends on the patient's attitude to termination of pregnancy, which is strongly influenced by social and religious factors. However, the majority of patients are still unaware of the availability of PGD, due to a relative novelty of the procedure. So there is obvious need for increasing awareness of PGD both for couples at risk and the medical profession, who require information about benefits, accuracy, safety, and expected risks of the procedure.

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